Antisense Bcl-2 oligodeoxynucleotides inhibit progression to androgen-independence after castration in the Shionogi

H Miyake1, A Tolcher, M E Gleave

  • 1The Prostate Centre, Vancouver General Hospital, British Columbia, Canada.

Cancer Research
|August 27, 1999
PubMed

Insights

Antisense Bcl-2 oligodeoxynucleotide (ODN) therapy effectively reduced Bcl-2 expression in prostate cancer cells. This approach delayed androgen-independent recurrence in a mouse model, showing potential for adjuvant prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Androgen-independence is a major challenge in advanced prostate cancer treatment.
  • Bcl-2 is upregulated in prostate cancer cells during progression to androgen-independence.
  • Targeting Bcl-2 offers a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the efficacy of antisense Bcl-2 oligodeoxynucleotide (ODN) therapy.
  • To determine if adjuvant antisense Bcl-2 ODN therapy can delay androgen-independent recurrence after castration.
  • To assess the specificity of antisense Bcl-2 ODN in prostate cancer models.

Main Methods:

  • In vitro treatment of Shionogi tumor cells with antisense Bcl-2 ODN.
  • Systemic administration of antisense Bcl-2 ODN in mice with androgen-dependent Shionogi tumors postcastration.
  • Monitoring tumor regression and emergence of androgen-independent recurrent tumors.
  • Assessing Bcl-2 expression in tumor tissues and normal mouse organs.

Main Results:

  • Antisense Bcl-2 ODN inhibited Bcl-2 expression in a dose-dependent and sequence-specific manner in vitro.
  • Systemic antisense Bcl-2 ODN treatment led to more rapid tumor regression.
  • A significant delay in the emergence of androgen-independent recurrent tumors was observed.
  • Antisense Bcl-2 ODN reduced Bcl-2 expression in tumors but not in normal organs.

Conclusions:

  • Antisense Bcl-2 ODN therapy is effective in reducing Bcl-2 expression in prostate cancer cells.
  • Adjuvant antisense Bcl-2 ODN therapy can delay androgen-independent recurrence in prostate cancer.
  • This therapy shows potential for use alongside androgen ablation in prostate cancer treatment.